MRI-guided HIFU-mediated heating and lesion formation enhanced with phase-shift nanoemulsions MRI-guided high intensity focused ultrasound (HIFU) has shown promise as a method for destroying solid tumors noninvasively through thermal mechanisms. While HIFU can destroy localized malignancies via the formation of lesions (i.e. coagulated tissue) with a high degree of spatial precision, it can take hours to treat an entire tumor. This has limited the efficiency of MRI-guided HIFU cancer therapy, and has hindered its acceptance clinically. It has been demonstrated that acoustic cavitation (i.e. acoustically-driven bubbles) can increase the efficiency of MRI-guided HIFU mediated heating and lesion formation in tissue. We have developed a phase-shift nanoemulsion (PSNE) to serve as nuclei for acoustic cavitation. By accumulating preferentially in solid tumors, the PSNE localize bubble nuclei to the diseased tissue. The PSNE can be vaporized acoustically, and the resultant bubbles can be used to accelerate ultrasound-mediated heating, thus reducing the time required for treatment of bulk tumors. We have designed a series of studies to evaluate the effectiveness of the strategy for localizing bubble-enhanced heating and producing predictable lesions in solid tumors. Finally, MR imaging and thermometry can be used to monitor bubble-enhanced HIFU-mediated heating, ensure that the required thermal dose for thermal ablation is delivered, and predict the lesion volume and location. PUBLIC HEALTH RELEVANCE: Cancer is the second leading cause of death in the United States. The research outlined in this proposal will develop technology and protocols for localized treatment of solid tumors using focused ultrasound with negligible adverse side effects. Ultimately, this technology has the potential to reduce the time and number of treatments required for tumor regression, thus reducing costs and improving cancer patient care.